Is the dawn of "gene doping" at hand?

LONDON - Scientists are racing to develop a test to catch athletes who may attempt to boost performance by manipulating their genes.

The premise is that athletes will use gene therapy techniques, using retroviral vectors, to amp up the expression of certain performance-enhancing genes. So the anti-doping folks want to screen for antibodies:

At the World Anti-Doping Association, researchers are trying to track the immune traces left by the viruses commonly used in gene doping. Gene transfers are most effectively performed with viruses, which have had any dangerous properties removed. In most cases, viruses tend to leave behind incriminating antibodies.

This is the same principle that incriminated Floyd Landis' urine samples -- it wasn't the presence of a high testosterone level, it was the presence of an isotopic signature (supposedly) distinctive to synthetic testosterone. (I should mention, I believe Landis is innocent, but his case makes a very convenient example.)

There is a certain comical aspect to this. The article describes how the anti-doping people are trying to find ways to characterize alterations in expression for "families" of genes:

Because it is virtually impossible to identify the individual gene altered, researchers are also focusing on the secondary impact such changes would provoke.

"If you perturb a biological system, you'll get all kinds of changes in the homeostasis to keep it functioning," Friedmann said.

Friedmann and his colleagues are researching a gene doping test in mice that attempts to identify the molecular changes following a gene mutation.

"We're finding families of genes that unexpectedly change in response to an alteration at the genetic level," Friedmann said. "Those genes can constitute a molecular signature for the system having been disturbed."

Now it is undoubtedly true that an attempt to amp up some regulatory gene in order to improve performance will cause changes to the expression of a large network of genes. But I find the article ludicrous for two reasons:

1. This cascade of changes is, of course, precisely the same kind of effect that systematic training in some sport should inspire compared to ordinary, non-elite athlete people. And we don't have a clue what those changes are at the genetic level! So first, you have to start with a sample of non-elite athletes and see what changes when you train intensively. Those changes will be heterogenous to some extent between different athletes (otherwise, they would all perform the same...). So you have to characterize the normal variability as an outcome of this highly unusual training regime. Only then can you start to assess whether a competitor is "outside the range" of normal variation. The Landis example makes it clear that we aren't at this point yet for ordinary chemical differences -- his testosterone tested high, but not outside the normal range.

2. The same problems that keep us from finding a good way to identify gene doping also pretty much prevent anybody from applying it. The anti-doping people don't know what genes will be targeted, because it is not at all obvious which genes doping should target. There is no "Olympic athlete HapMap". Heck, we don't even know how to gene dope a horse (Max Zorin notwithstanding), and for horses at least someone would probably absorb the costs of experimentation. These anti-doping people are working on mice, for goodness' sake.

The article is focused on the Beijing Olympics, with the idea that blood samples will be kept afterward for 10 years, so tests could be developed in the far future to detect current cheating.

But there is a total lack of recognition of a basic reality: Somebody who actually could figure out how to genetically enhance an athlete before 2008 probably deserves a Nobel prize! And if they could figure that out, they would be a paid a whole lot more by applying their 'l33t genetic skillz curing osteoporosis or something.

Not to say there aren't candidates -- for instance, suppose you could ratchet down a weightlifter's myostatin to match this kid. It is not too complicated to make it work, it's just that it won't be made to work in the next couple of years. The trickle-down from gene therapy is inevitable, but gene therapy itself is far from being ready yet.

I mean, really, the reason why any reasonably talented scientist would deal in routine chemical enhancement for athletes is either (a) the black market and need for silence makes it incredibly lucrative compared to treating growth disorders in private practice, or (b) a much-higher-than-usual athlete-wanna-be complex. As soon as we do make some progress on these genetic systems, there will be plenty of doctors standing in line to do it. Just not so many Nobel-prize-worthy scientists. I mean, even Zorin's doctor had that whole residual-Third-Reich-loyalty keeping him in the game.

Keep in mind, that many of these genetic manipulations will be most effective as interventions early in childhood, maximizing the developmental alteration. A huge shift in gene expression a year before the Olympics will usually be a lot less effective than a small course correction in a five-year-old. And are Olympic anti-doping mavens going to start screening out people because they had a small tweak in HGH when they were toddlers?

The real theme of the article seems to be an attempt to scare athletes into shying away from gene doping. All the talk about health risks, and changing Mother Nature's blueprints, and whatnot -- they end with a warning that gene transfer may cause cancer by activating oncogenes.

But really, there are plenty of people who would stand in line to trade 20 years of their lives to win an Olympic medal. And many who think that the current winners are simple beneficiaries of a genetic lottery. As soon as genetic modifications become routine to correct developmental problems, the kids who had them will start coming up through the sports ranks. The way it stands now, the Olympics and other sports venues are staging themselves as some of the last arbiters of "pure" humanity.

John Hawks is the Vilas-Borghesi Distinguished Achievement Professor of Anthropology at the University of Wisconsin—Madison. I work on the fossil and genetic record of human evolution (About me).

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